Department of Oncology and Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Research Building, Room E504, 3970 Reservoir Rd., NW, Washington D. C. 20057, USA.
Department of Oncology and Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Research Building, Room E504, 3970 Reservoir Rd., NW, Washington D. C. 20057, USA; Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington D. C. 20057, USA.
Life Sci Space Res (Amst). 2022 Nov;35:53-59. doi: 10.1016/j.lssr.2022.09.005. Epub 2022 Sep 15.
A significantly higher probability of space radiation-induced gastrointestinal (GI) cancer incidence and mortality after a Mars mission has been projected using biophysical and statistical modeling approaches, and may exceed the current NASA mandated limit of less than 3% REID (risk of exposure-induced death). Since spacecraft shielding is not fully effective against heavy-ion space radiation, there is an unmet need to develop an effective medical countermeasure (MCM) strategy against heavy-ion space radiation-induced GI carcinogenesis to safeguard astronauts. In the past, we have successfully applied a GI cancer mouse model approach to understand space radiation-induced GI cancer risk and associated molecular signaling events. We have also tested several potential MCMs to safeguard astronauts during and after a prolonged space mission. In this review, we provide an updated summary of MCM testing using the GI cancer mouse model approach, lessons learned, and a perspective on the senescence signaling targeting approach for desirable protection against space radiation-induced GI carcinogenesis. Furthermore, we also discuss some of the advanced senotherapeutic candidates/combinations as a potential MCM for space radiation-induced GI carcinogenesis.
采用生物物理和统计建模方法预测，火星任务后发生空间辐射诱导胃肠道（GI）癌症的概率和死亡率显著增加，可能超过当前 NASA 规定的小于 3%REID（暴露诱导死亡风险）的限值。由于航天器屏蔽对重离子空间辐射并非完全有效，因此需要开发针对重离子空间辐射诱导 GI 致癌的有效医疗对策（MCM）策略，以保护宇航员。过去，我们成功地应用了 GI 癌症小鼠模型方法来了解空间辐射诱导的 GI 癌症风险和相关的分子信号事件。我们还测试了几种潜在的 MCM，以在长时间太空任务期间和之后保护宇航员。在这篇综述中，我们提供了使用 GI 癌症小鼠模型方法进行 MCM 测试的最新总结、经验教训以及针对空间辐射诱导 GI 致癌的衰老信号靶向方法的观点。此外，我们还讨论了一些先进的衰老治疗候选物/组合作为针对空间辐射诱导 GI 致癌的潜在 MCM。
